title: Adenosine-A3 receptors in neutrophil microdomains promote the formation of bacteria-tethering cytonemes.
abstract: The A3-adenosine receptor (A3AR) has recently emerged as a key regulator of neutrophil behaviour. Using a fluorescent A3AR ligand, we show that A3ARs aggregate in highly polarized immunomodulatory microdomains on human neutrophil membranes. In addition to regulating chemotaxis, A3ARs promote the formation of filipodia-like projections (cytonemes) that can extend up to 100 μm to tether and 'reel in' pathogens. Exposure to bacteria or an A3AR agonist stimulates the formation of these projections and bacterial phagocytosis, whereas an A3AR-selective antagonist inhibits cytoneme formation. Our results shed new light on the behaviour of neutrophils and identify the A3AR as a potential target for modulating their function.
authors.affiliation: Institute of Cell Signalling, School of Biomedical Sciences, Medical School, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: Ross
authors.initials: R
authors.lastname: Corriden
authors.forename: Tim
authors.initials: T
authors.lastname: Self
authors.forename: Kathryn
authors.initials: K
authors.lastname: Akong-Moore
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Barrie
authors.initials: B
authors.lastname: Kellam
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Briddon
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Hill
mesh_terms: D021961:Cell Membrane Structures / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure*; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008024:Ligands; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure*; D010587:Phagocytosis / Q000187:drug effects; D011485:Protein Binding; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D043684:Receptor, Adenosine A3 / Q000378:metabolism*
chemical_list: D008024:Ligands; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3